Gamma-aminobutyric acid type B receptor subunit 1
Also known as: GABBR1, GPRC3A
Function
Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.
Classification
- Family (Pfam)
- PF00003 7tm_3, PF01094 ANF_receptor, PF00084 Sushi
- InterPro
- ANF_lig-bd_rcpt, GPCR3_GABA-B, GPCR_3_C, GPCR_3_GABA_rcpt_B1, Peripla_BP_I, Sushi/SCR/CCP_sf, Sushi_SCR_CCP_dom
- Functional cluster
- Mixed Regulatory & Membrane Proteins
Experimental structures · PDB · 24
- 4MQE X-ray 2.35A
- 4MQF X-ray 2.22A
- 4MR7 X-ray 2.15A
- 4MR8 X-ray 2.15A
- 4MR9 X-ray 2.35A
- 4MRM X-ray 2.86A
- 4MS1 X-ray 2.25A
- 4MS3 X-ray 2.50A
- 4MS4 X-ray 1.90A
- 4PAS X-ray 1.62A
- 6HKC NMR
- 6UO8 EM 3.63A
- … and 12 more
A predicted model is available from AlphaFold.
Gene Ontology · 35
- GO:0030673 axolemma
- GO:0043198 dendritic shaft
- GO:0043197 dendritic spine
- GO:0005789 endoplasmic reticulum membrane
- GO:0005615 extracellular space
- GO:0038039 G protein-coupled receptor heterodimeric complex
- GO:1902710 GABA receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0098978 glutamatergic synapse
- GO:0031966 mitochondrial membrane
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0042734 presynaptic membrane
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0008021 synaptic vesicle
- GO:1990430 extracellular matrix protein binding
- GO:0004965 G protein-coupled GABA receptor activity
- GO:0099579 G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential
- GO:0150047 G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential
- GO:0046982 protein heterodimerization activity
- GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:0008285 negative regulation of cell population proliferation
- GO:0033602 negative regulation of dopamine secretion
- GO:0032811 negative regulation of epinephrine secretion
- GO:0014053 negative regulation of gamma-aminobutyric acid secretion
- GO:0050805 negative regulation of synaptic transmission
- GO:0150099 neuron-glial cell signaling
- GO:0001649 osteoblast differentiation
- GO:0014049 positive regulation of glutamate secretion
- GO:0060124 positive regulation of growth hormone secretion
- GO:0045471 response to ethanol
- GO:0035094 response to nicotine
- GO:0051932 synaptic transmission, GABAergic
Disease associations
Drugs targeting this protein · 9
- SGS-742 antagonist
- SODIUM OXYBATE agonist
- ARBACLOFEN PLACARBIL agonist
- ARBACLOFEN agonist
- LESOGABERAN agonist
- CALCIUM OXYBATE agonist
- MAGNESIUM OXYBATE agonist
- POTASSIUM OXYBATE agonist
- BACLOFEN agonist
Related proteins · sequence + function similarity
- Gamma-aminobutyric acid type B receptor subunit 1 1.00
- Gamma-aminobutyric acid type B receptor subunit 1 1.00
- Glutamate receptor ionotropic, NMDA 1 0.85
- Glutamate receptor ionotropic, NMDA 1 0.84
- Glutamate receptor ionotropic, NMDA 1 0.84
- Glutamate receptor ionotropic, NMDA 1 0.84
- Glutamate receptor ionotropic, NMDA 1 0.81
- Corticotropin-releasing hormone receptor 1 0.79
- Corticotropin-releasing hormone receptor 1 0.79
- Corticotropin-releasing hormone receptor 1 0.79
- Corticotropin-releasing hormone receptor 1 0.78
- Sodium/hydrogen exchanger 8 0.78
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid type B receptor subunit 2 9 shared papers
- Gamma-aminobutyric acid type B receptor subunit 1 4 shared papers
- Gamma-aminobutyric acid type B receptor subunit 1 3 shared papers
- Gamma-aminobutyric acid type B receptor subunit 2 3 shared papers
- Gamma-aminobutyric acid type B receptor subunit 2 1 shared papers
- Janus kinase and microtubule-interacting protein 1 1 shared papers
- Janus kinase and microtubule-interacting protein 1 1 shared papers
- Janus kinase and microtubule-interacting protein 1 1 shared papers
Literature · 20 cited papers
- GABBR1 monoallelic de novo variants linked to neurodevelopmental delay and epilepsy. Am. J. Hum. Genet. · 2022
- Structural mechanism of ligand activation in human GABA(B) receptor. Nature · 2013
- Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat. Neurosci. · 2012
- Direct detection of the interaction between recombinant soluble extracellular regions in the heterodimeric metabotropic gamma-aminobutyric acid receptor. J. Biol. Chem. · 2008
- Subcellular distribution of GABA(B) receptor homo- and hetero-dimers. Biochem. J. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- An unappreciated role for RNA surveillance. Genome Biol. · 2004
- Marlin-1, a novel RNA-binding protein associates with GABA receptors. J. Biol. Chem. · 2004
- The DNA sequence and analysis of human chromosome 6. Nature · 2003
- Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J. Biol. Chem. · 2000
- Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor. J. Pharmacol. Exp. Ther. · 2000
- Association analysis of exonic variants of the gene encoding the GABAB receptor and idiopathic generalized epilepsy. Am. J. Med. Genet. · 1999
- … and 8 more in the literature graph